The modifier-of-deaf waddler (mdfw) is a hearing susceptibility locus which confers progressive hearing loss to CBy-dfw2J/+ heterozygous. Neither homozygosity at the mdfw locus nor heterozygosity at the dfw2J locus alone are sufficient to cause the observed hearing impairment indicating a synergistic interaction between the two loci. Recently, we identified the dfw gene and showed that mutations in the plasma membrane Ca2+ ATPase 2 gene (Atp2b2) are the cause of hearing loss and imbalance in two mutant strains of deaf waddler. We are now focusing on identifying the second component (mdfw) of this genetic interaction. Using a positional cloning approach we attempt to identify the mdfw gene. During the last year we expanded the mapping cross and constructed an integrated genetic, radiation hybrid and BAC based physical map of markers around mdfw. We fine mapped mdfw to a small genetic and physical interval. During the last year we sample sequenced non-recombinant BAC clones and are now in the process of evaluating candidate genes.